Fig. 1

Temporal association of immune dysfunction syndromes. After an initial combat-related injury, there is the development of a hyper-inflammatory response, termed the systemic inflammatory response syndrome (SIRS), and an immune suppressing response, termed the compensatory anti-inflammatory response syndrome (CARS). These two responses happen within minutes to days, occurring nearly simultaneously, and it is during these initial inflammatory phases that death from early multi-organ dysfunction syndrome (MODS) may occur. As both the pro-inflammatory and anti-inflammatory responses resolve, there is a period of resolution, typically within days to weeks, that allows for the return to homeostasis and survival after the injury. However, in a percentage of injured patients, the pro-inflammatory and/or anti-inflammatory responses never resolve, leading to a period of chronic critical illness termed persistent inflammatory-immunosuppressive and catabolic syndrome (PICS). This occurs in patients who have been critically ill for longer than 14 days with significant lymphopenia and chronic inflammation. PICS may persist for months and lead to the risk of developing later MODS and secondary infections with subsequent morbidity and late mortality